Risk factors for advanced prostate cancer are poorly understood, but appear to differ from risk factors for occult disease. Although previous studies implicate both genetic and dietary factors in prostate cancer progression, attributable risk estimates for any single factor are not high. The possibility that genetic susceptibility might be expressed only in combination with dietary or other environmental exposures is the focus of this proposal. By examining genetic and dietary influences together, we may be able to identify important risk factors that are obscured when genes or diet are examined in isolation. Specifically, we hypothesize that allelic variation in genes controlling proliferation (androgen pathway genes) and differentiation (the vitamin D receptor gene) of prostate epithelium will influence risk of advanced prostate cancer, and that risk will be further modified by environmental (especially dietary) factors. We will address the following questions. 1. Are polymorphisms in androgen pathway genes associated with risk of advanced prostate cancer? 2. Does dietary fat or fiber intake modify risk of advanced prostate cancer among men with high- or low-risk genotypes? 3. Are polymorphisms in the vitamin D receptor gene associated with risk of advanced prostate cancer? 4. Does dietary calcium intake or vitamin D status (as measured by sunlight exposure and dietary intake) modify risk of advanced prostate cancer among men with high- or low-risk VDR genotypes? To address these questions, we propose to conduct a case-control study of 1000 men with advanced prostate cancer (500 Latino and 500 non-Latino white) ascertained through the Los Angeles County Cancer Surveillance Program, using neighborhood controls. Dietary and risk-factor questionnaires and blood samples will be collected. Odds ratios and effect modification will be evaluated using standard epidemiologic methods.